Prostate cancer accounts for one-fourth of all cancer diagnoses in men in the United States, with an estimated 192,280 new cases in 2009 (1). Although most men will have an indolent form of the disease, aggressive prostate cancers are currently the second leading cause of cancer deaths in men in the United States. Most cases of prostate cancer are diagnosed as a result of having an elevated serum level of prostate-specific antigen (PSA). PSA-based disease screening leading to early detection and treatment of prostate cancer (PCa) has contributed to the reduction in mortality observed for this disease in the United States over the past several years (1). However, results from two large randomized trials in Europe and the US provide strong evidence that PSA-based screening for PCa is associated with a high risk of overdiagnosis (2,3). In the European trial, PSA screening was associated with decreased PCa related mortality but at a great cost: ˜1,410 men needed to be screened, and 48 additional PCa cases would need to be treated to prevent one death from PCa (2). Although interpretation of these findings is still a subject of discussion, the current inability to accurately distinguish risk for life-threatening, aggressive PCa from the overwhelming majority of indolent cases contributes to the dilemma.
Recent breakthroughs in genome-wide association studies (GWAS) have led to the discovery of more than two dozen reported single nucleotide polymorphisms (SNPs) that are associated with PCa risk by comparing men with and without PCa using case-control study designs (6-25). Unfortunately, none of these PCa risk associated SNPs consistently distinguishes risk for more or less aggressive cancer (26-28), nor are they associated with prostate cancer-specific mortality (29). As a result, there has been much debate regarding the clinical utility of these SNPs as a risk stratification tool (30,31). Clearly, an alternative approach is needed to identify genetic markers that distinguish those men who are at risk for developing more aggressive PCa.
The present invention overcomes previous shortcomings in the art by identifying significant statistical associations between genetic markers and prostate cancer. Thus, the present invention provides methods and compositions for identifying a subject at increased risk of developing aggressive prostate cancer by detecting the genetic markers of this invention in the subject.